Ex-Collingwood champion Percy Wilson was appointed Melbourne's captain-coach in an attempt to boost the team into the finals for the first time since 1915, and while they finished two games out of the four it was a significantly improved performance compared to 1920 when they had fired early then fallen apart for the rest of the year.

Two factions vied for control of the club at the start of the year - the 1920 committee of Harry Parkin, Vin Coutie, L. Nichols, G. Pope, Wally Sykes, G. Couttar and C. Couchman were challenged by a reform group of HD Westley, C. Finlay, K. Batten, C. Brady, H. Ritchie and GH Watson. G. Strickland ran as an independent candidate.

1921 was the first time scores from other grounds were displayed at each match, with codes to decipher the scores available in the Football Record.

The Round 5 match against St Kilda ended in a protest which claimed Melbourne had been wrong given a point and should have lost. Unlike St Kilda's Round 1, 1900 win on protest their efforts at getting the result changed were unsuccessful.

In July Melbourne were scheduled to play a match in Colac but pulled out in the week of the game.